PROJECT SUMMARY A core criterion used to diagnose alcohol use disorders is the continued consumption of alcohol in the face of negative consequences. These consequences may include negative impact on work productivity, health, and interpersonal relationships. Preclinical animal models have been developed to study this and other behaviors that are observed in patients with addictive disorders. To study consumption despite negative consequences, the model of aversion-resistant alcohol intake has been developed. In this procedure, alcohol access is paired with a negative stimulus, usually either footshock punishment or quinine adulteration (a bitter tastant that rodents find highly aversive). The quinine adulteration model has been used in the last several years to examine the pharmacology and neurocircuitry of aversion resistant alcohol intake. However, the vast majority of these studies used male mice only. Our recent studies suggest that female mice show decreased sensitivity to quinine adulteration, suggesting that they are more aversion-resistant than male mice and may have a higher propensity for compulsive-like alcohol intake. This proposal examines this sex difference, first determining the role of circulating sex hormones in this behavioral phenotype and then examining the specific brain regions that mediate this effect. Examination of addiction-related behaviors using female subjects is of critical importance as we know far less about these processes in females due to the fact that studies in addiction biology have primarily used male animals. The outcomes of these experiments will help to further our understanding of the mechanisms that contribute to alcohol abuse in females and will open new avenues for medications development.